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Equations are derived for the precision of least-squares estimates of mono-exponential decay times from optical measurements containing both photon shot noise and background noise. The special case of data containing only photon shot noise leads to the same equation as that derived previously by others using the maximum likelihood estimation method. It is shown that for a sufficiently large number of data points used in the fit, spanning up to approximately ten decay times, the lifetime estimate precision reaches a limit value being the inverse square root of the number of photons contained in the decay curve used for the estimate. Further, an extension to the general case where both types of noise are present is provided. Approximating photon statistical noise as normally distributed, the expressions for precision are shown to be valid even for very low signal-to-noise ratios. Thus, the theory provides a straightforward and useful tool to assess the lifetime estimate precision from a single decay measurement. [ABSTRACT FROM AUTHOR]

Background: Previous analyses have shown that long-acting risperidone (LAR) is cost-effective in several Western countries. In Portugal, however, the costs of key services are lower. Therefore, available evidence in other countries may have limited relevance.Objective: To estimate costs and effects of LAR versus a conventional depot and a short-acting oral atypical antipsychotic over a 5-year period in Portugal.Methods: An existing discrete event model was adapted to reflect the Portuguese healthcare setting, based on expert opinion, clinical, epidemiological, and cost data. The model compares three scenarios. In scenario 1, patients start with a conventional depot; in scenario 2, with LAR; and in scenario 3, with oral risperidone. The model simulates individual patient histories while taking into account patient characteristics such as risk to society and side-effects. Subsequently, the model simulates patient histories in terms of outpatient appointments, psychotic episodes, treatment, compliance, symptom scores, lack of ability to take care presenting an actual risk, and treatment setting. Outcomes were number of psychotic episodes, cumulative symptom score and direct medical costs. Univariate sensitivity analyses were carried out.Results: Compared to a conventional depot and an oral atypical, LAR was estimated to save approximately euro 3603 and euro 4682 per patient (respectively) and avoid 0.44 and 0.59 relapses per patient in 5 years. Sensitivity analyses showed that the outcome of dominance was only sensitive to estimates about unit costs of hospital/institutionalization, potential risk, and to the reduction in symptoms by use of atypicals.Conclusion: Based on this modeling exercise, it could be expected that LAR may be a cost-effective treatment with limited budget impact in Portugal. However, further studies are required to test the generalizability of the results of the present modeling study to the larger population of Portugal. [ABSTRACT FROM AUTHOR]

The requirements for obtaining cryogenic temperatures (i.e. 150 K and below) by anti-Stokes fluorescence cooling are analysed for a dielectric cooling medium located inside the cavity of a diode-pumped solid state laser. The cooling efficiency is derived in terms of pump beam parameters, intracavity loss associated with the cooling medium, reabsorption and saturation effects in the gain medium, radiative and conductive heat load on the cooling medium, and finally bulk and surface heating effects. Using experimental data for a Yb 3+ :ZrF 4 –BaF 2 –LaF 3 –AlF 3 –NaF [ZBLAN] cooling medium and a Yb 3+ :KY(WO4) 2 [KYW] gain medium, the conditions for optimum cooling efficiency are obtained. Based on realistic materials properties, the analysis shows that it is feasible to obtain a cooling efficiency (i.e. cooling power per input diode pump power) of approximately 0.1% at an operating temperature of 150 K, with a heat lift up to 30 mW. [ABSTRACT FROM AUTHOR]

To improve the accuracy in MCMs, progression-free survival (PFS) cure rates or published mature OS data can be used as priors to inform OS. The validation data closest resembled the survival predictions of the MCM with priors, followed by Weibull and MCM without priors. [Extracted from the article]

The aim of this study is to explore three methods for extrapolating survival: PNMA, spline NMA, and a novel mixture-cure PNMA (MCPNMA) methodology. Weibull distribution was fitted on the trial data using the standard PNMA, spline NMA and MCPNMA methodologies. MCPNMA and spline NMA had better fit over the trial data than PNMA. [Extracted from the article]

Abstract Background As schizophrenia patients are typically suspicious of, or are hostile to changes they may be reluctant to accept generic substitution, possibly affecting compliance. This may counteract drug costs savings due to less symptom control and increased hospitalization risk. Although compliance losses following generic substitution have not been quantified so far, one can estimate the possible health-economic consequences. The current study aims to do so by considering the case of risperidone in Germany. Methods An existing DES model was adapted to compare staying on branded risperidone with generic substitution. Differences include the probability of non-compliance and medication costs. Incremental probability of non-compliance after generic substitution was varied between 2.5% and 10%, while generic medication costs were assumed to be 40% lower. Effect of medication price was assessed as well as the effect of applying compliance losses to all treatment settings. The probability of staying on branded risperidone being cost-effective was calculated for various outcomes of a hypothetical study that would investigate non-compliance following generic substitution of risperidone. Results If the incremental probability of non-compliance after generic substitution is 2.5%, 5.0%, 7.5% and 10% respectively, incremental effects of staying on branded risperidone are 0.004, 0.007, 0.011 and 0.015 Quality Adjusted Life Years (QALYs). Incremental costs are €757, €343, -€123 and -€554 respectively. Benefits of staying on branded risperidone include improved symptom control and fewer hospitalizations. If generic substitution results in a 5.2% higher probability of non-compliance, the model predicts staying on branded risperidone to be cost-effective (NICE threshold of ₤30,000 per QALY gained). Compliance losses of more than 6.9% makes branded risperidone the dominant alternative. Results are sensitive to the locations at which compliance loss is applied and the price of generic risperidone. The probability that staying on branded risperidone is cost-effective would increase with larger compliance differences and more patients included in the hypothetical study. Conclusion The model predicts that it is cost-effective to keep a patient with schizophrenia in Germany on branded risperidone instead of switching him/her to generic risperidone (assuming a 40% reduction in medication costs), if the incremental probability of becoming non-compliant after generic substitution exceeds 5.2%.

Objective: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA).A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed.The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC.InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.Materials and methods: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA).A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed.The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC.InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.Results: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA).A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed.The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC.InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.Conclusions: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA).A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed.The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC.InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings. [ABSTRACT FROM AUTHOR]